Chen Sang

Publications (2)6.75 Total impact

• Article: Effects of stress fiber contractility on uniaxial stretch guiding mitosis orientation and stress fiber alignment.

  Lei Zhao, Chen Sang, Chun Yang, Fengyuan Zhuang
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  ABSTRACT: It has been documented that mitosis orientation (MO) is guided by stress fibers (SFs), which are perpendicular to exogenous cyclic uniaxial stretch. However, the effect of mechanical forces on MO and the mechanism of stretch-induced SFs reorientation are not well elucidated to date. In the present study, we used murine 3T3 fibroblasts as a model, to investigate the effects of uniaxial stretch on SFO and MO utilizing custom-made stretch device. We found that cyclic uniaxial stretch induced both SFs and mitosis directions orienting perpendicularly to the stretch direction. The F-actin and myosin II blockages, which resulted in disoriented SFs and mitosis directions under uniaxial stretch, suggested a high correlation between SFO and MO. Y27632 (10 μM), ML7 (50 μM, or 75 μM), and blebbistatin (50 μM, or 75 μM) treatments resulted in SFO parallel to the principle stretch direction. Upon stimulating and inhibiting the phosphorylation of myosin light chain (p-MLC), we observed a monotonic proportion of SFO to the level of p-MLC. These results suggested that the level of cell contraction is crucial to the response of SFs, either perpendicular or parallel, to the external stretch. Showing the possible role of cell contractility in tuning SFO under external stretch, our experimental data are valuable to understand the predominant factor controlling SFO response to exogenous uniaxial stretch, and thus helpful for improving mechanical models.
  Journal of biomechanics 09/2011; 44(13):2388-94. · 2.66 Impact Factor
• Source

  Available from: PubMed Central

  Article: Epimorphin regulates bile duct formation via effects on mitosis orientation in rat liver epithelial stem-like cells.

  Junnian Zhou, Lei Zhao, Lipeng Qin, Jing Wang, Yali Jia, Hailei Yao, Chen Sang, Qinghua Hu, Shuangshuang Shi, Xue Nan, Wen Yue, Fengyuan Zhuang, Chun Yang, Yunfang Wang, Xuetao Pei
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  ABSTRACT: Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3alpha and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, beta1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role.
  PLoS ONE 01/2010; 5(3):e9732. · 4.09 Impact Factor